title: A novel activation-induced cytidine deaminase (AID) mutation in Brazilian patients with hyper-IgM type 2 syndrome.
abstract: Activation-induced cytidine deaminase (AID) is a DNA editing protein that plays an essential role in three major events of immunoglobulin (Ig) diversification: somatic hypermutation, class switch recombination and Ig gene conversion. Mutations in the AID gene (AICDA) have been found in patients with autosomal recessive Hyper-IgM (HIGM) syndrome type 2. Here, two 9- and 14-year-old Brazilian sisters, from a consanguineous family, were diagnosed with HIGM2 syndrome. Sequencing analysis of the exons from AICDA revealed that both patients are homozygous for a single C to G transversion in the third position of codon 15, which replaces a conserved Phenylalanine with a Leucine. To our knowledge, this is a new AICDA mutation found in HIGM2 patients. Functional studies confirm that the homologous murine mutation leads to a dysfunctional protein with diminished intrinsic cytidine deaminase activity and is unable to rescue CSR when introduced in Aicda(-/-)stimulated murine B cells. We briefly discuss the relevance of AICDA mutations found in patients for the biology of this molecule.
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, n° 6, 2780-156 Oeiras, Portugal. nadine.caratao@gmail.com
authors.forename: Nadine
authors.initials: N
authors.lastname: Caratão
authors.forename: Catarina S
authors.initials: CS
authors.lastname: Cortesão
authors.forename: Pedro H
authors.initials: PH
authors.lastname: Reis
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Freitas
authors.forename: Cristina M A
authors.initials: CM
authors.lastname: Jacob
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Pastorino
authors.forename: Magda
authors.initials: M
authors.lastname: Carneiro-Sampaio
authors.forename: Vasco M
authors.initials: VM
authors.lastname: Barreto
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001938:Brazil / Q000453:epidemiology; D002648:Child; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: AID; APOBEC1; Activation-induced cytidine deaminase; CSR; GC; Hyper-immunoglobulin M; Mutation; NES; NLS; PI; SHM; activation-induced cytidine deaminase; apolipoprotein B mRNA editing catalytic polypeptide 1; class switch recombination; gene conversion; hAID; human AID; nuclear export signal; nuclear localization signal; propidium iodide; somatic hypermutation; wild type; wt